Steric repulsion introduced by loop constraints modulates the microphase separation of chromatins.

Within the confines of a densely populated cell nucleus, chromatin undergoes intricate folding, forming loops, domains, and compartments under the governance of topological constraints and phase separation. This coordinated process inevitably introduces interference between different folding strategies. In this study, we model interphase chromatins as block copolymers with hetero-hierarchical loops within a confined system. Employing dissipative particle dynamics simulations and scaling analysis, we aim to explain how the structure and distribution of loop domains modulate the microphase separation of chromatins. Our results highlight the correlation between the microphase separation of the copolymer and the length, heterogeneity, and hierarchically nested levels of the loop domains. This correlation arises from steric repulsion intrinsic to loop domains. The steric repulsion induces variations in chain stiffness (including local orientation correlations and the persistence length), thereby influencing the degree of phase separation. Through simulations of block copolymers with distinct groups of hetero-hierarchical loop anchors, we successfully reproduce changes in phase separation across diverse cell lines, under fixed interaction parameters. These findings, in qualitative alignment with Hi-C data, suggest that the variations of loop constraints alone possess the capacity to regulate higher-order structures and the gene expressions of interphase chromatins.

Osmotic Pressure and Its Biological Implications.

Gaining insight into osmotic pressure and its biological implications is pivotal for revealing mechanisms underlying numerous fundamental biological processes across scales and will contribute to the biomedical and pharmaceutical fields. This review aims to provide an overview of the current understanding, focusing on two central issues: (i) how to determine theoretically osmotic pressure and (ii) how osmotic pressure affects important biological activities. More specifically, we discuss the representative theoretical equations and models for different solutions, emphasizing their applicability and limitations, and summarize the effect of osmotic pressure on lipid phase separation, cell division, and differentiation, focusing on the mechanisms underlying the osmotic pressure dependence of these biological processes. We highlight that new theory of osmotic pressure applicable for all experimentally feasible temperatures and solute concentrations needs to be developed, and further studies regarding the role of osmotic pressure in other biological processes should also be carried out to improve our comprehensive and in-depth understanding. Moreover, we point out the importance and challenges of developing techniques for the in vivo measurement of osmotic pressure.

Tuning cell adhesion on supported lipid bilayers via nanoscale geometry.

The cell-supported lipid bilayer (SLB) adhesion system has been widely used as the model system to study the receptor-ligand interactions that occur at the membrane interface. The ligand-functionalized SLBs are deposited either directly on solids or on polymer cushions. An important question that arises is whether the geometry of the SLB affects the binding of cell adhesion receptors to the ligands. By using a mesoscopic mechanical model and Monte Carlo simulations, we have investigated the adhesion of a fluid membrane to a corrugated or egg-carton shaped SLB. We find that the nanoscale geometry of the SLB strongly affects the receptor-ligand binding. This effect results from the fact that the adhering membrane bends according to the SLB geometry in order for the adhesion receptors to bind ligands. The membrane bending couples with spatial distribution of the receptor-ligand complexes and membrane thermal undulations. Our results demonstrate that cell adhesion to SLBs can be controlled by tuning the nanoscale geometry of the SLB, and may have profound implications for future development of tissue engineering and regenerative medicine.

Bacterial agents and changes in drug susceptibilities in cases of chronic dacryocystitis, Southern China.

PURPOSE: This study aimed to determine the susceptibility and the changes of bacterial agents of chronic dacryocystitis and determine the risk factors for bacterial prevalence and drug sensitivity to provide a reference for clinical selection of antibiotics. METHODS: A case-control study was conducted using 112 patients with chronic dacryocystitis and 112 patients with non-infectious ophthalmopathy between August 2017 and April 2018. Lacrimal and conjunctival sac secretions were cultured for aerobic and anaerobic bacteria. Forty-five patients with chronic dacryocystitis between November 2014 and November 2015 were also included. RESULTS: Positive bacterial cultures were obtained from 61.9% and 50.9% of chronic dacryocystitis and non-infectious ophthalmopathy patients, but the detection rates for pathogenic bacteria were 18.3% and 2.7%, respectively (P > 0.001). Gram-negative and anaerobic bacteria were significantly more prevalent in the patient group compared with the control group (P = 0.001 and 0.005, respectively). Bacteria were detected at a significantly higher rate in patients with irritant symptoms (itch or foreign-body sensation) than in those without (OR = 9.333, P = 0.002), particularly Staphylococcus (OR = 9.783, P = 0.002). 11.6% (10/86) and 55.8% (48/86) showed resistance to levofloxacin and tobramycin, respectively. Compared with three years ago, the detection rate for Gram-positive cocci decreased from 51.1% to 27.8% (χ2 = 8.054, P = 0.005) CONCLUSIONS: Gram-positive cocci, Gram-negative bacilli, and anaerobic bacteria were the predominant pathogens. The prevalence of Gram-positive bacteria in cases of chronic dacryocystitis is decreasing.

Confined space self-propagating room temperature synthesis of carbon-encapsulated Fe3O4 nanocrystals and its lithium storage performance.

A self-propagating reaction between ferrocene and iron nitrate nonahydrate that is initiated at room temperature is discovered. Amorphous carbon-encapsulated Fe3O4 nanocrystals (Fe3O4@C) can be one-step prepared in an autoclave through this reaction. The equiaxed Fe3O4 nanocrystals have typical dimensions in the range of 5-60 nm with a median size of 24.1 nm, and their weight percent is up to 82.3%. The course of the reaction is recorded, and the formation mechanism of Fe3O4@C with the core-shell structure is proposed. The scaling-up synthesis is also achieved, and 52.1 g of the Fe3O4@C can be obtained in a single batch. The shock wave appeared in the fast gas release self-propagating reaction in confined space plays a decisive role in the preparation of homogeneous Fe3O4@C with a core-shell structure. The Fe3O4@C anode shows excellent capacity retention with a high specific capacity of 494 mAh g-1 at 1 A g-1 in the 200th cycle.

Nanobubbles in confined solution: Generation, contact angle, and stability.

The formation of gas bubbles presents a frequent challenge to microfluidic operations, for which fluids are geometrically confined to a microscale space. Here, to understand the mechanism of nucleating gas bubbles in microfluidic devices, we investigate the formation and stability of nanobubbles in confined solutions. Our molecular dynamics simulations show that while pinning of the contact line is a prerequisite for the stability of surface nanobubbles in open systems that can exchange gas with surrounding environment, in confined solutions, stable nanobubbles can exist even without pinning. In supersaturated condition, stable bubbles can be found in confined solutions with acute or obtuse contact angle, depending on the substrate hydrophobicity. We also demonstrate that when open to the bulk solution, the stable nanobubbles in closed systems would become unstable unless both supersaturation and pinning of the contact line are satisfied. Our results not only shed light on the design of novel heterogeneous surfaces for generating nanobubbles in confined space with controllable shape and stability but also address the crucial effect of gas exchange with the surroundings in determining the stability of nanobubbles.

Lipid rafts enhance the binding constant of membrane-anchored receptors and ligands.

Gaining insights into the binding of membrane-anchored receptors and ligands that mediate cell adhesion and signal transduction is of great significance for understanding numerous physiological processes driven by intercellular communication. Lipid rafts, microdomains in cell membranes enriched in cholesterol and saturated lipids such as sphingomyelin, are believed to serve as the essential platforms to recruit protein molecules for biological functions. An important question remains how the lipid rafts affect the binding constant of membrane-anchored receptors and ligands. We have investigated the adhesion of multicomponent membranes by using Monte Carlo simulations of a mesoscopic model with biologically relevant parameters. We find that the preferential partitioning of membrane-anchored receptor and ligand proteins in the lipid rafts significantly increases the binding constant of those proteins, in cooperation with the shape fluctuations of the membranes caused by thermal excitations. The binding constant can even be greater than that of the same receptors and ligands anchored to two apposing supported, planar membranes without shape fluctuations. The membrane shape fluctuations facilitate the binding of the anchored receptors and ligands, in contrast to the case of homogeneous membranes. Our results suggest that cells might regulate the binding of membrane-anchored receptor and ligand proteins by modulating the properties of lipid rafts such as area fraction, size and the affinity of rafts to the proteins.

Highly efficient one-step synthesis of carbon encapsulated nanocrystals by the oxidation of metal π-complexes.

Various carbon encapsulated nanocrystals, including MnS and MnO, Cr2O3, MoO2, Fe7S8 and Fe3O4, and ZrO2, are prepared in one step and in situ by a simple and highly efficient synthesis approach. The nanocrystals have an equiaxed morphology and a median size smaller than 30 nm. Tens and hundreds of these nanocrystals are entirely encapsulated by a wormlike amorphous carbon shell. The formation of a core-shell structure depends on the strongly exothermic reaction of metal π-complexes with ammonium persulfate in an autoclave at below 200 °C. During the oxidation process, the generated significant amounts of heat will destroy the molecular structure of the metal π-complex and cleave the ligands into small carbon fragments, which further transform into an amorphous carbon shell. The central metal atoms are oxidized to metal oxide/sulfide nanocrystals. The formation of a core-shell structure is independent of the numbers of ligands and carbon atoms as well as the metal types, implying that any metal π-complex can serve as a precursor and that various carbon encapsulated nanocrystals can be synthesized by this method.

Two-dimensional measurements of receptor-ligand interactions.

Gaining insight into the two-dimensional receptor-ligand interactions, which play a significant role in various pivotal biological processes such as immune response and cancer metastasis, will deepen our understanding of numerous physiological and pathological mechanisms and contribute to biomedical applications and drug design. A central issue involved is how to measure the in situ receptor-ligand binding kinetics. Here, we review several representative mechanical-based and fluorescence-based methods, and briefly discuss the strengths and weaknesses for each method. In addition, we emphasize the great importance of the combination of experimental and computational methods in studying the receptor-ligand interactions, and further studies should focus on the synergistic development of experimental and computational methods.

[Preliminary study of Boston keratoprosthesis in treatment of severe late stage ocular chemical burns].

OBJECTIVE: To evaluate preliminary clinical outcome of Boston type I keratoprosthesis in ocular chemical burn patients. METHODS: Six keratoprosthesis were implanted into 6 patients of bilateral blindness. Visual acuity in these patients before the operation was light perception and all of them were unsuitable for standard penetrating corneal transplantation. The causes for corneal opacity were alkali burn in 2, sulfate acid burn in 3 and ethanol injury in 1 patient. Shirmer's test revealed severe dry eye in 3 patients, only one eye had normal lacrimal secretion. All patients were male, with follow-up period ranged from 17 to 26 months (mean 24 months). RESULTS: The postoperative visual acuity ranged from 0.05 to 0.5, 5 of them was better than 0.1. The retention rate within the follow-up period was 100%. Intraocular pressure was in normal limit, no retinal detachment was detected by type B ultrasonic examination. Postoperatively, retro-keratoprosthestic membrane occurred in 2 cases and was treated with YAG laser membranectomy, one eye complicated with elevated intraocular pressure and treated with shunt implantation. CONCLUSION: The Boston type 1 keratoprosthesis is a viable option for patients with obsolete chemical burns.

Topological Constraints with Optimal Length Promote the Formation of Chromosomal Territories at Weakened Degree of Phase Separation.

It is generally agreed that the nuclei of eukaryotic cells at interphase are partitioned into disjointed territories, with distinct regions occupied by certain chromosomes. However, the underlying mechanism for such territorialization is still under debate. Here we model chromosomes as coarse-grained block copolymers and to investigate the effect of loop domains (LDs) on the formation of compartments and territories based on dissipative particle dynamics. A critical length of LDs, which depends sensitively on the length of polymeric blocks, is obtained to minimize the degree of phase separation. This also applies to the two-polymer system: The critical length not only maximizes the degree of territorialization but also minimizes the degree of phase separation. Interestingly, by comparing with experimental data, we find the critical length for LDs and the corresponding length of blocks to be respectively very close to the mean length of topologically associating domains (TADs) and chromosomal segments with different densities of CpG islands for human chromosomes. The results indicate that topological constraints with optimal length can contribute to the formation of territories by weakening the degree of phase separation, which likely promotes the chromosomal flexibility in response to genetic regulations.

Interplay Between Receptor-Ligand Binding and Lipid Domain Formation Depends on the Mobility of Ligands in Cell-Substrate Adhesion.

Cell-cell adhesion and the adhesion of cells to extracellular matrix are mediated by the specific binding of receptors on the cell membrane to their cognate ligands on the opposing surface. The adhesion receptors can exhibit affinity for nanoscale lipid clusters that form in the cell membrane. Experimental studies of such adhesion systems often involve a cell adhering either to a solid surface with immobile ligands or a supported lipid bilayer with mobile ligands. A central question in these cell-substrate adhesions is how the mobility of the ligands physically affects their binding to the adhesion receptors and thereby the behavior of the nanoscale lipid clusters associated with the receptors. Using a statistical mechanical model and Monte Carlo simulations for the adhesion of cells to substrates with ligands, we find that, for mobile ligands, binding to adhesion receptors can promote the formation of mesoscale lipid domains, which in turn enhances the receptor-ligand binding. However, in the case of immobile ligands, the receptor-ligand binding and the tendency for the nanoscale lipid clusters to further coalesce depend on the distribution of the ligands on the substrate. Our findings help to explain why different adhesion experiments for identifying the interplay between receptor-ligand binding and heterogeneities in cell membranes led to contradictory results.

Effects of the Laplace pressure on the cells during cytokinesis.

The Laplace pressure is one of the most fundamental regulators that determine cell shape and function, and thus has been receiving widespread attention. Here, we systemically investigate the effect of the Laplace pressure on the shape and function of the cells during cytokinesis. We find that the Laplace pressure during cytokinesis can directly control the distribution and size of cell blebbing and adjust the symmetry of cell division by virtue of changing the characteristics of cell blebbing. Further, we demonstrate that the Laplace pressure changes the structural uniformity of cell boundary to regulate the symmetry of cell division. Our findings provide further insights as to the important role of the Laplace pressure in regulating the symmetry of cell division during cytokinesis.

Enhanced thermal shock resistance of ceramics through biomimetically inspired nanofins.

We propose here a new method to make ceramics insensitive to thermal shock up to their melting temperature. In this method the surface of ceramics was biomimetically roughened into nanofinned surface that creates a thin air layer enveloping the surface of the ceramics during quenching. This air layer increases the heat transfer resistance of the surface of the ceramics by about 10,000 times so that the strong thermal gradient and stresses produced by the steep temperature difference in thermal shock did not occur both on the actual surface and in the interior of the ceramics. This method effectively extends the applications of existing ceramics in the extreme thermal environments.

[The effects of transplantation of compound keratoprosthesis in clinical practice and managements of complications after operation].

OBJECTIVE: To explore the clinical value and management of complications of the transplantation of Titanium skirt compounded keratoprosthesis for severe corneal blindness eyes. METHODS: It was a retrospective case series study. Nine eyes from 9 male patients, aged 28 to 52 years old, accepted permanent keratoprosthesis transplantation in Zhongshan Ophthalmic Center from March 2002 to June 2005. All patients had corneal lesion in both eyes for 1.5 to 5.0 years. Among the 9 treated eyes, 6 eyes was severe vascularization after alkali burns, 3 eyes explosive injuries. Light perception was remained in all patients before surgery, however, 2 eyes only had a questionable orientation of light perception among them. Surgical management was divided into two stages. In the first stage, transplantation of Titanium skirt compound keratoprosthesis was performed, and the explant was reinforced by the self auricular cartilage and Tendons capsule. The second stage of surgery was performed in 5 to 6 months later, in which the membrane in the front of keratoprosthesis was cut. After the surgery, visual acuity, visual field, intraocular pressure and retina were examined. The complications were noticed and managed. RESULTS: All treated eyes were followed up for 1 to 3 years. After the treatment, 7 eyes divorced from blindness with uncorrected visual acuity 20/200 (0.1), and 2 eyes among them got corrected visual acuity 20/30 (0.6). Two eyes with the questionable orientation of light perception before treatment gained uncorrected visual acuity 4/200 (0.02) and 8/200 (0.04) after treatment respectively. Complications were found to include 5 recurrent frontal membrane of keratoprosthesis, one back membrane of keratoprosthesis, and one limited corneal melting. Complications were controlled by the corresponding treatments, such as membrane resection for the recurrent frontal membrane of keratoprosthesis, courage under microscope for back membrane of keratoprosthesis, and reinforcement of acellular dermis for corneal melting. All keratoprosthesis were maintained in situ, and no rejection and leakage of aqueous humor happened. CONCLUSIONS: It is effective to use transplantation of keratoprosthesis for the severe corneal blindness eyes. Combination with self auricular cartilage and Tendons capsular reinforcement may reduce the complications and improve the biocompatibility of keratoprosthesis.

Efficacy and Safety of Transglutaminase-Induced Corneal Stiffening in Rabbits.

PURPOSE: To evaluate the biomechanical efficacy and safety of in vivo microbial transglutaminase (Tgases)-induced corneal crosslinking in a rabbit model. METHODS: A total of 34 white New Zealand rabbits were divided into two groups, a biochemistry group and a photochemistry group. The right eye of every rabbit was treated and left eyes served as negative controls. In the biochemistry group, a 1 U/mL solution of crosslinking agent microbial Tgases (Tgases CXL) was applied to the corneal surface, while in the photochemistry group, clinical ultraviolet A-riboflavin crosslinking (UVA/RF CXL) was used. Efficacy and safety evaluated on the 14th day after the procedures. Twelve pairs of corneal strips were harvested from the eyes of 12 euthanized rabbits in every group, and uniaxial tensile tests were performed to evaluate ex vivo biomechanical effects. The CXL-treated eye to its corresponding untreated eye ratio of tangent modulus were calculated. Another five pairs of corneal button were excised from euthanized animals in every group for corneal stroma and endothelium staining to evaluate changes in keratocyte distribution and endothelial cell damage. RESULTS: In tensile tests, tangent modulus was statistically higher in the Tgases CXL groups under 1.0 MPa (26.59 ± 4.54 vs. 21.47 ± 4.72 MPa, P = 0.04) and 1.5 MPa (29.75 ± 5.01 vs. 20.47 ± 6.63 MPa, P = 0.00). The tangent modulus ratio of Tgases group (1.72 ± 1.0 vs. 1.05 ± 0.22, P = 0.04) was significantly higher than that of UVA/RF under 1.5-MPa stress. The distribution of keratocytes in the corneal stroma and the morphologies of endothelial cells were similar in Tgases CXL-treated and untreated corneas. However, in the UVA/RF CXL group, keratocytes in the anterior half of stromal thickness were lost, and clear endothelial cell apoptosis was observed. CONCLUSIONS: Tgases-CXL effectively stiffened the cornea and caused no damage to the endothelium and keratocytes in the cornea. This crosslinking method could be useful as a next-generation treatment for corneal ectasia and could replace CXL of photochemistry. TRANSLATIONAL RELEVANCE: These findings may give a new hope to biomechanically compromised corneal disease due to mechanical forces, such as corneal ectasia and keratoconus. A next-generation treatment to these corneal diseases due to mechanical forces may be designed based on the new findings.

[Preliminary outcome of large-diameter lamellar keratoplasty combined with deep lamellar endothelial keratoplasty for whole cornea destruction].

OBJECTIVE: To understand the indication, surgical principle, outcome and complications of large-diameter lamellar keratoplasty combined with deep lamellar endothelial keratoplasty for whole cornea destruction. METHODS: Eleven hospitalized patients with whole cornea destruction in Zhongshan Ophthalmic Center, Sun Yat-Sen University from May, 2005 to March, 2006 were involved in this study. Five left eyes and six right eyes underwent large-diameter lamellar keratoplasty combined with deep lamellar endothelial keratoplasty. The patients were followed up for 12 to 18 months and their pinhole postoperative visual acuity, intraocular pressure, pachymetry of the central cornea and corneal endothelial cell density was recorded. RESULTS: The pinhole postoperative visual acuity of all patients improved and averaged separately 4.4 +/- 0.3, 4.5 +/- 0.3 and 4.5 +/- 0.3 at the 3rd, 6th and 12th postoperative month. There was a temporary increase of the postoperative intraocular pressure within one postoperative week which can be controlled by medication and released soon. And the postoperative intraocular pressure averaged (19.8 +/- 2.7), (19.2 +/- 1.7) and (19.5 +/- 2.0) mm Hg respectively at the 3rd, 6th and 12th month postoperatively. At the same following up times, the pachymetry of the central cornea averaged (538.9 +/- 8.9), (536.3 +/- 6.3) and (537.2 +/- 6.9) microm respectively and the corneal endothelial cell density averaged (2519.8 +/- 110.7), (2244.4 +/- 137.9) and (2093.3 +/- 141.9) cells/mm2 respectively. The main complication was the interspace between the two lamellar grafts and it would disappear automatically within one postoperative month. CONCLUSIONS: Large-diameter lamellar keratoplasty combined with deep lamellar endothelial keratoplasty can avoid postoperative glaucoma. It may offer further advantages over traditional surgery to treat whole cornea destruction.

[Preliminary clinical study of sutureless, small-incision deep lamellar endothelial keratoplasty surgery].

OBJECTIVE: To investigate the surgical procedure, clinical efficacy, and the prevention and management of complications of sutureless, small-incision deep lamellar endothelial keratoplasty (DLEK). METHODS: Nine patients (nine eyes) with bullous keratopathy underwent sutureless, small-incision DLEK surgery, six of them was combined with anterior vitrectomy. Visual acuity, graft clearance, corneal curvature, astigmatism and endothelial cell density (ECD) were observed over a 3 - 5 month follow-up period. RESULTS: All grafts remained transparent, and six eyes had improved visual acuity. After the surgery, mean corneal curvature was (43.96 +/- 3.38) D. Mean corneal astigmatism was (3.32 +/- 1.20) diopter (D). Mean ECD was (2124 +/- 278) cells/mm(2). No severe complications occurred. CONCLUSION: Sutureless, small-incision DLEK, as compared with penetrating keratoplasty (PKP) and microkeratome-associated deep lamellar endothelial keratoplasty, has more advantages and is expected to be the initial surgical treatment for bullous keratopathy.

[Microkeratome-assisted deep lamellar endothelial keratoplasty].

OBJECTIVE: To observe the indication, surgical principle, clinical results and complications of microkeratome-assisted deep lamellar endothelial keratoplasty (DLEK). METHODS: DLEK was performed in six patients with bullous keratopathy. One of the six patients underwent DLEK combined with vitrectomy under temporary artificial corneal and intraocular foreign-body removal. Another underwent DLEK combined with vitrectomy and posterior chamber intraocular lens implantation. The patients were followed up for 6 approximately 9 months. RESULTS: The postoperative best-corrected visual acuity showed clear improvement in 5 cases. Endothelial cell density averaged (2481 +/- 212) cells/mm(2). Pachymetry averaged (549 +/- 61) micro m. Astigmatism averaged (2.04 +/- 1.19) D. No serious complication was found. CONCLUSION: DLEK is an alternative choice for PKP. It may offer further advantages over conventional PKP surgery, and could serve as a surgical technique in endothelial keratoplasty. A long-term follow-up in a larger patient population is needed to confirm our initial results.

The effects of ageing on the biomechanical properties of root dentine and fracture.

OBJECTIVES: Knowledge of the mechanical behaviour of root dentine can facilitate better understanding of spontaneous vertical root fracture (VRF), an age-related disease initiated mainly at the root apex. We tested the hypothesis that the biomechanical properties of root dentine change with ageing. METHODS: Sixteen human premolars were divided into "old" (17-30 years) and "young" (50-80 years) groups. The elastic modulus, nano-hardness, micro-hardness, elemental contents, tubular density/area of root dentine in cervical, middle and apical root regions were evaluated using atomic force microscopy-based nano-indentation, Knoop indentation, scanning electron microscopy and energy dispersive X-ray spectroscopy, respectively. RESULTS: The apical dentine showed a lower nano-hardness, a lower elastic modulus, a lower calcium content, a lower calcium-to-phosphorus ratio and a smaller tubular density/area than the cervical dentine in both age groups, whereas spatial differences in micro-hardness were observed only in old roots. Compared with young dentine, old dentine showed a greater hardness, a higher elastic modulus, a greater mineral content and a smaller tubular size in the cervical portion, whereas the age-induced changes in tubular density were insignificant. Finite element analysis revealed that due to its higher elastic modulus, old apical dentine has a higher stress level than young dentine. CONCLUSIONS: The intrinsic material properties of root dentine have spatial variations, and they are altered by ageing. The higher stress level in old apical dentine may be one reason, if not the most important one, why spontaneous VRFs are more likely to occur in the elderly population.